Ion mobility spectrometry (IMS) is a gas-phase ion separation technique in which ions become separated in time as they travel through a drift cell (drift tube) of known length containing a buffer gas (drift gas) of known composition (e.g., nitrogen), pressure and temperature. During this travel, the ions become separated based on their different collision cross sections (CCSs), which can be correlated to their differing mobilities through the buffer gas. An IMS system in general includes an ion source for ionizing molecules of a sample of interest, followed by the drift cell that receives the ions, followed by an ion detector for counting the separated ions. The ion detector communicates with electronics configured for processing output signals from the ion detector as needed to produce a user-interpretable drift spectrum. The drift spectrum is typically presented as a plot containing a series of peaks indicative of the relative abundances of detected ions as a function of their drift time through the drift cell. The drift spectrum may be utilized to identify and distinguish different analyte species of the sample.
IMS may be coupled with one or more other types of separation techniques to increase compound identification power, such as gas chromatography (GC), liquid chromatography (LC), or mass spectrometry (MS). For example, an IMS drift cell may be coupled in-line with an MS system to form a combined IM-MS system. An MS system in general includes a mass analyzer for separating ions based on their differing mass-to-charge ratios (or m/z ratios, or more simply “masses”), followed by an ion detector. An MS analysis produces a mass spectrum, which is a series of peaks indicative of the relative abundances of detected ions as a function of their m/z ratios. The mass spectrum may be utilized to determine the molecular structures of components of the sample. An IMS drift cell is often coupled to a time-of-flight mass spectrometer (TOF MS), which utilizes a high-resolution mass analyzer (TOF analyzer) in the form of an electric field-free flight tube. An ion extractor (or pulser) injects ions in pulses (or packets) into the flight tube. Ions of differing masses travel at different velocities through the flight tube and thus separate (spread out) according to their differing masses, enabling mass resolution based on time-of-flight.
In the combined IM-MS system, the ion source is followed by the IMS drift cell, which is followed by the mass analyzer and then the ion detector. Thus, ions are separated by mobility prior to being transmitted into the MS where they are then mass-resolved. Performing the two separation techniques in tandem is particularly useful in the analysis of complex chemical mixtures, including biopolymers such as polynucleotides, proteins, carbohydrates and the like, as the added dimension provided by the IM separation may help to separate ions that are different from each other but present overlapping mass peaks. This hybrid separation technique may be further enhanced by coupling it with LC, thus providing an LC-IM-MS system.
In low-field drift-time IMS techniques, ions travel through the drift cell under the influence of a uniform DC voltage gradient established by electrodes of the drift cell. Typical electric fields utilized for low-field IMS techniques include, but are not limited to, 10 to 20 V/cm, and typical buffer gas pressures include, but are not limited to, 1 to 760 Torr. While the electric field moves the ions through the drift cell, the ions experience a drag force due to collisions with the stationary buffer gas molecules in the drift cell. The drag force acts against the electrical force that moves the ions. The drag force experienced by an ion depends on its collision cross section (CCS or Ω), which is a function of the size and shape of the ion, and on its electrical charge and mass. Multiply charged ions move through the buffer gas more effectively than singly charged ions because multiply charged ions experience a greater force due to the electrical field. Ions with larger CCSs are retarded more easily by collisions with the buffer gas. After entering the drift cell, an equilibrium state between the drag force and electrical force is quickly reached and the ions start moving with constant drift velocity Vd, which is proportional to the applied electric field of strength E as follows:Vd=KE,  (1)
where the proportionality constant K is the gas phase mobility of an ion, typically given in units of cm2×V−1×s−1. To account for differences in the pressure and temperature of the buffer gas, the mobility K may be expressed as reduced mobility Ko in which the pressure P (in Torr) and temperature T (in Kelvin) of the buffer gas are normalized, as follows:
                                          K            O                    =                                    L                                                t                  d                                ⁢                E                                      ⁢                          P              760                        ⁢                          273.2              T                                      ,                            (        2        )            
where the ion drift velocity is expressed in terms of the length L of the drift cell and the drift time td (in ms) of the ion through the drift cell, 760 Torr is standard pressure, and 273.2 Kelvin is standard temperature. Thus, the mobility of an ion of interest may be calculated experimentally by measuring the ion's drift time td, i.e., the time taken by the ion to traverse the drift cell of known length L and applied electric field strength E.
If the drift time of an ion through the drift cell, the pressure in the drift cell, and the voltage across the drift cell are known, then one can calculate the CCS of the ion. This CCS parameter is specific for the ion and is instrument-independent, and therefore can be utilized as a unique parameter for compound identification. The CCS parameter is of great interest in structural characterization of molecules, theoretical molecular dynamic simulations, and other fields of inquiry. Reduced mobility Ko can be related to CCS, Ω (typically in Angstroms squared, Å2), through the Mason-Schamp equation:
                                          K            O                    =                                                                      (                                      18                    ⁢                    π                                    )                                                  1                  /                  2                                            16                        ⁢                                                            ze                                                            (                                                                        k                          b                                                ⁢                        T                                            )                                                              1                      /                      2                                                                      ⁡                                  [                                                            1                                              m                        I                                                              +                                          1                                              m                        B                                                                              ]                                                            1                /                2                                      ⁢                          1              N                        ⁢                          1              Ω                                      ,                            (        3        )            
where ze is the charge on the ion, kb is the Boltzmann constant, T is the temperature, mI the mass of the ion, mB is the mass of the buffer gas molecule, and N is the number density of the buffer gas. It is seen that ion mobility is directly proportional to the charge on the ion and inversely proportional to the CCS of the ion. The CCS may be calculated directly from experimentally determined variables such as drift time td by combining equations (2) and (3) and solving for Ω, as follows:
                    Ω        =                                                            (                                  18                  ⁢                  π                                )                                            1                /                2                                      16                    ⁢                                                    ze                                                      (                                                                  k                        b                                            ⁢                      T                                        )                                                        1                    /                    2                                                              ⁡                              [                                                      1                                          m                      I                                                        +                                      1                                          m                      B                                                                      ]                                                    1              /              2                                ⁢                                                    t                d                            ⁢              E                        L                    ⁢                      760            P                    ⁢                      T            273.2                    ⁢                                    1              N                        .                                              (        4        )            
In a typical ion mobility based system, there is some distance over which an ion travels from the exit of the drift cell to the ion detector, and over which the ion's flight is not appreciably influenced by mobility. For example, in a hybrid IM-MS system it takes additional time for an ion to reach the detector due to ion optical elements existing between the drift cell and the mass analyzer/detector. Thus, the observed drift time of an ion as measured by the detector, tD, is greater than the actual time the ion took to travel through the drift cell, td. Thus, the drift time td utilized in the Mason-Schamp equation to calculate the CCS of the ion is a “corrected” drift time, which may be found from the following relation:td=tD−t0,  (5)
where t0 is the time the ion spent traveling from the exit of the drift cell to the ion detector. The proper calculation of time t0 is crucial for the accuracy of CCS measurements.
Conventionally, time t0 is calculated by performing several ion mobility experiments at different drift field strengths, E (V/cm) and plotting observed (measured) drift time tD (y-axis) over the inverse of the applied drift voltage (1/V) (or over field strength (1/E)) (x-axis). The resulting plot is a set of data points (1/V, tD) lying along a straight line showing the linear correlation between observed drift time and inverse applied drift field/voltage. The intercept of this plot with the y-axis (drift time axis) is the time t0 for the ion of interest.
The common practice is to employ at least five different drift voltages and perform at least five ion mobility experiments (frames) at each drift voltage for one CCS experiment. Assuming it takes about 60 ms to perform one ion mobility experiment, the total measurement time required would be about 1.5 s. Unfortunately, such an amount of measurement time is unacceptably long for many situations. For example, such an amount of measurement time is not very compatible with modern chromatography, as the chromatographic peak width may be as short as 1 s, with peak widths of 3 s being quite common.
Therefore, there is a need for providing a method for faster CCS measurement, particularly one that is compatible with the time scale of chromatographic separation.